Downregulated LncRNA-ANCR promotes osteoblast differentiation by targeting EZH2 and regulating Runx2 expression

Biochem Biophys Res Commun. 2013 Mar 22;432(4):612-7. doi: 10.1016/j.bbrc.2013.02.036. Epub 2013 Feb 21.

Abstract

Long noncoding RNAs (lncRNAs) are key regulators of diverse biological processes such as transcriptional regulation, cell growth and differentiation. Previous studies have demonstrated that the lncRNA-ANCR (anti-differentiation ncRNA) is required to maintain the undifferentiated cell state within the epidermis. However, little is known about whether ANCR regulates osteoblast differentiation. In this study, we found that the ANCR expression level is significantly decreased during hFOB1.19 cell differentiation. ANCR-siRNA blocks the expression of endogenous ANCR, resulting in osteoblast differentiation, whereas ANCR overexpression is sufficient to inhibit osteoblast differentiation. We further demonstrated that ANCR is associated with enhancer of zeste homolog 2 (EZH2) and that this association results in the inhibition of both Runx2 expression and subsequent osteoblast differentiation. These data suggest that ANCR is an essential mediator of osteoblast differentiation, thus offering a new target for the development of therapeutic agents to treat bone diseases.

MeSH terms

  • Cell Differentiation / genetics*
  • Cell Line
  • Core Binding Factor Alpha 1 Subunit / antagonists & inhibitors
  • Core Binding Factor Alpha 1 Subunit / genetics*
  • Down-Regulation
  • Enhancer Elements, Genetic
  • Enhancer of Zeste Homolog 2 Protein
  • Gene Expression Regulation*
  • Humans
  • Osteoblasts / cytology*
  • Polycomb Repressive Complex 2 / genetics*
  • Promoter Regions, Genetic
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*

Substances

  • ANCR long noncoding RNA, human
  • Core Binding Factor Alpha 1 Subunit
  • RNA, Long Noncoding
  • RUNX2 protein, human
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Polycomb Repressive Complex 2